The objective of this research is to study the viral and the cellular control of the transformed phenotype in cells transformed by the oncogenic viruses polyoma and SV40. We also want to study the mechanism of viral DNA integration, and the functions controlling its rearrangements in the transformed cells. Our work is planned along three main lines of research: 1) The study of viral and cellular factors controlling the association between the viral and the cellular genome in rat cells transformed by polyoma virus. In this system, "free" and integrated viral DNA molecules coexist, and the free molecules result from excision and limited replication of the integrated viral DNA. Excision requires an active viral A-gene product, and generates "cured", which have lost an integral number of viral DNA molecules. Amplification of integrated viral DNA can also occur in the presence of a functional large T antigen. We will study the mechanisms and requirements of excision and amplification. 2) The study of the modalities and requirements for the primary integration event in polyoma infection of rat cells. 3) The study of the evolution of integrated viral DNA sequences in polyoma transformed cells, and its relationship with the expression of transforming or recombination functions.